I. Field of the Invention
Embodiments of this invention are directed generally to biology and medicine. In certain embodiments the invention is directed to compositions and method of using multitype HPV polypeptides.
II. BACKGROUND
Genital-tropic human papillomavirus (HPV) infections are considered the most common sexually transmitted infection in the United States (CDC Report to Congress, Prevention of Genital Human Papillomavirus Infection, January 2004). The major manifestations of anogenital HPV include genital warts (condyloma acuminatum) and intraepithelial neoplasia of the vulva, cervix, anus, or penis. A small fraction of persistent high-risk HPV infections, if left untreated, progresses to cancer. (e.g., cervical cancer, on occasion head and neck cancer, and some types of non-melanoma skin cancer). The presence of HPV DNA has been reported in 99.7% of cervical carcinomas worldwide, suggesting that HPV infection is a necessary cause of this cancer and that this disease can be prevented by prophylactic HPV vaccination (Walboomers et al., 1999).
In addition to genital warts, HPV infection can result in common warts, plantar warts, or planar warts. Warts may exist in different forms depending on the HPV type responsible and the epithelium involved. Common warts (verruca vulgaris) usually occur on the hands, as flesh-colored to brown, exophytic, and hyperkeratotic papules. Plantar warts (verruca plantaris) occur on the soles of the feet and can be quite painful. They can be differentiated from calluses by removing the surface layer to reveal thrombosed capillaries. Flat or planar warts (verruca plana) are most common among children and can occur on the face, neck, chest and flexor surfaces of the forearms and legs.
Approximately 35 of the more than 100 subtypes of HPV are specific for the anogenital epithelium and have varying potentials for malignant transformation (Munoz et al., 2003). Of the 15 oncogenic genital HPV types, HPV16 is the most common, followed by HPV 18 and HPV45 (contributing ˜50%, ˜20% and ˜10% of cervical cancer cases, respectively). Despite the successes of public health efforts to reduce the incidence and mortality of cervical cancer with the implementation of cervical cytology screening programs, women who do not undergo regular screening account for most of the patients with invasive cancers (Hoffman and Cavanagh, 1995) and cervical cancer remains the second most common cause of cancer death in women worldwide and the most prevalent cancer in women of sub-Saharan Africa, Central America, south-central Asia and Melanesia (a subregion of Oceania extending from the western side of the West Pacific to the Arafura Sea, north and northeast of Australia; the term was first used to denote an ethnic and geographical grouping of islands distinct from Polynesia and Micronesia) (Parkin, 2001). Approximately 471,000 cases of invasive cervical carcinoma are diagnosed annually (Parkin, 2001).
The HPV genome is surrounded by a 60-nm, non-enveloped icosahedral capsid (Baker et al., 1991) which contains the two genetically-unrelated major capsid protein L1 and the minor capsid protein L2. Recombinant L1 self-assembles into virus-like particles (VLPs) which are morphologically and immunologically similar to native virions (Kirnbauer et al., 1992). L1 VLP-based vaccines are highly protective against infection corresponding to the papillomavirus type used to derive the immunogen (homologous vaccine), but are ineffective against all but the most closely related HPV types (Roden et al., 2000). Licensed HPV vaccines have circumvented this obstacle by designing multivalent vaccine preparations; CERVARIX™ contains L1 VLP derived from HPV16 and HPV18, while GARDASIL™ also contains HPV6 and HPV11 L1 VLPs for prevention of benign genital warts. Unfortunately, the expense and the need for refrigeration of these L1 VLP vaccines currently renders them impractical for use in low resource and remote areas where they are most needed. Furthermore, because these vaccines are ineffective against a significant fraction of oncogenic HPV types, costly cytologic screening programs remain necessary. To realize the full potential of HPV prevention globally, the vaccine should be safe and effective, stable at ambient temperature to facilitate delivery in remote locations, inexpensive to manufacture, and administered without needles, preferably available in a single dose formulation. The disease burden resulting from the plethora of HPV types suggest that a broadly protective vaccine is necessary. Thus, there is a need for additional cross-neutralizing HPV vaccines.